Epigenetics: of mice and men and women.

This is the second of two posts on epigenetics.  In the first I was critical of using epigenetics to explain the transgenerational transmission of trauma.  In this post I am less critical, but the epigenetics of trauma remains a research project in its early stages.  The ACE test (adverse childhood experience), available now, is a better use of epigenetics.

The epigenetic scaffold

It used to be thought that the chemical scaffold that surrounded the DNA double-helix was unimportant.  Today scientists recognize its importance.  This scaffold is called the epigenome (epi from the Greek for above), and is composed of proteins and other chemicals.  The scaffold chemically tells a gene whether to turn on or off.  A gene that is turned off is like no gene at all.  Experience in the world effects the epigenome, which means that the experience of trauma, or more accurately susceptibility to trauma, can be genetically transmitted in the same way other traits, such as hair color, are genetically transmitted.

Two mechanisms are particularly important for gene silencing.  DNA methylation and histone modification.  DNA methylation is the best-known example of a mitotically (referring to cell division) heritable epigenetic modification.  (Ennis, loc 354).  Unlike DNA methylation, most scientists thought that histone modification patterns weren’t copied directly to the new chromosomes produced during mitosis (cell division). However, a study by Susan Strome showed that some of the original strand’s modified histones are passed to the newly forming strand during DNA replication (Ennis, loc 354, 422).  Other studies have confirmed this result.

It seems clear that epigenetic changes brought about by experiences such as trauma may be transmitted to subsequent generation during the process of reproduction.  Whatever else is discovered about the epigenome, it is no longer makes sense to distinguish sharply between nature and nurture.  Still, we should not become overenthusiastic.  Strome’s study was done with worms; most are done with mice or rats.

Lick your babies, or someone else’s

How well and often rat mothers lick their babies (grooming behavior it’s called) during the first ten days of life predicts changes in the pups’ stress response that lasts for a lifetime.

Even more startling,  the changes continued into the next generation, because female pups who had high-licker moms became high lickers themselves when they had their own kids.  (Harris, p 81)

But how to determine whether the pups who became good licker mommies did so because they inherited a genetic change in the mother rat, or because they learned to be good groomers from the experience of being well-licked?  One experiment implanted newly impregnated zygotes in surrogate mothers.  “The study found that the pups’ DNA methylation took on the pattern of their foster moms, not their genetic moms.” (Harris, p 85)  This would mean that young pups’ experience is changing the epigenome.

Culture

One difference between mice and men is that people have culture, and that makes a big difference in how babies are raised.  I lived for a while in Seoul, Korea.  A common item of clothing there, but one I have never seen here, is a winter coat sewn large enough so that a Korean mother could hold her baby next to her under the coat during the cold Korean winters. 

Koreans, like Japanese, believe that skin contact between mother and child is essential to socialization.  But whether skinship, as it is sometimes called, actually makes a difference in the security of adult Koreans and Japanese is virtually impossible to know.  So many cultural factors intervene between mother, father, and baby that it’s impossible to distinguish between (epi)gene and meme*, at least when we are talking about subtle expressions, such as resistance to stress-induced trauma.

One more experiment: stoned mice

Yasmin Hurd, a professor of neurobiology, exposed adolescent rats to THC (the active ingredient in marijuana).  After all the THC had left the rats’ bodies, Hurd and her associates allowed the stoner mice to mate with straight-living mice.  The resulting pups were given to clean-living foster mothers to raise.  When the pups matured the were presented with a device that required them to exert effort to get a dose of heroin.

Rats with a parent that had been exposed to THC were willing to put in more effort to obtain the drug . . . . A follow-up study in 2015 found brain-specific DNA methylation changes that correlate with altered patterns of gene transcription. (Ennis, loc 731)

I’m tempted to conclude that dope smoking mama mice bore mice with a stronger work-ethic, but this wasn’t Hurd’s conclusion.  In any case, it doesn’t matter.  It’s clear that in mouse models, as they are called, new experiences can be epigenetically transferred from one generation to the next (Ennis, loc 731-740).

How all this might be relevant now: ACE

It’s far too early to make claims about intergenerational transmission of a susceptibility to trauma in humans, even as some researchers are hardly able to resist the temptation.  This from the Journal of Traumatic Stress, the leading journal in the field.

Holocaust survivor offspring report childhood histories that are not incompatible with having had [rat] mothers who excessively “licked and groomed,” but unlike rodents, this cohort can articulate the subjective emotional consequences of such behaviors. (Yehuda and Bierer)

What epigenetics does do is reveal how childhood trauma lives on forever in the minds and bodies of the survivors, leading to significantly higher rates of death and disease.

The ACE study

ACE refers to adverse childhood experiences.  Nadine Harris tells the fascinating story of how it came into use.  One of the advantages of ACE studies is they can draw on data from a survey of 17,420 people, a huge gain in a field where the number studied is often in the low dozens or less (Felitti and Anda).  The questions asked are about gross adversities, such as losing a parent to death or divorce, having an imprisoned parent, being sexually abused, witnessing violence, and so forth.  (The questions and scoring are on pp 228-229 of Harris’ book.)

By the way, one might imagine that these are experiences characteristic of the ghetto.  In fact, the original ACE study was done on a middle-class population that was 70 percent Caucasian and 70 percent college educated.  Their average age was 57.  Almost all were employed, as they were members of Kaiser Permanente health insurance, which was able to track its members over a number of years.  Adverse childhood experiences are not absent in the middle-class; they are just better hidden.

The ACE Study strongly establishes a dose – response relationship, which is an important step toward demonstrating causality.  A person with an ACE score of seven or more has triple the lifetime odds of getting lung cancer and three and a half times the odds of having ischemic heart      disease  . . . . Apart from these revelations, the profound discovery was that our patients with four or more ACEs were twice as likely to be overweight or obese and 32.6 times as likely to have been diagnosed with learning and behavioral problems. (Harris, pp 40, 59)

In addition, people with an ACE score of four had a 240 percent greater risk of hepatitis, were 390 percent more likely to have chronic obstructive pulmonary disease, and a 240 percent higher risk of a sexually-transmitted disease. (Anda and Felitti)

The main way adverse childhood experiences affect adult health is through the almost constant activation of the stress response.

Activation of the stress response is one big way the environment can change epigenetic notations. As your body tries to adapt to the stress of your experiences, it turns certain genes on or off, particularly genes that regulate how you’ll respond to stressful events in the future.  That process of the epigenome working with the genome to respond to your environment is called epigenetic regulation and it’s critical to our understanding of why toxic stress is so damaging to our lifelong health.  There are a handful of processes that are responsible for epigenetic regulation, but the two that we know the most about when it comes to the genetics of stress are DNA methylation and histone modification. (Harris, p 83)

Conclusion

Even studies on humans rely on animal models for their hypotheses about how stress is transmitted over the life-cycle.  Nevertheless, the statistics are impressive, and it is unnecessary to speculate about the intergenerational transmission of trauma.  It’s enough to focus on one generation.  Trauma in the early life of one generation, perhaps even in utero, leads to stress-related illnesses as that generation ages.  Epigenetics goes some way to explaining how.

Even without an epigenetic explanation, the ACE studies are impressive.  Childhood trauma can become a chronic disease lasting a (often shortened) lifetime.  Furthermore, we know how to “cure” the disease by treating the trauma.  That we generally don’t is the sin of our generation, for once we know there is no excuse for not acting.

The limit to the ACE study is that it only monitors gross adversities.  A narcissistic mother, a psychologically distant father, overly anxious parents: these too result in adult mental and physical illness, only they are invisible to ACE.  Nevertheless, ACE has begun the conversation, and its incorporation in many physicians’ routine physicals is a good start.  Its wider use in schools and clinics is encouraging, but has a long way to go.

Epigenetics makes ACE and other approaches to trauma more intellectually interesting and exciting.  It’s closer to the cutting edge of psychological science.  But, if our goal is helping people now, then ACE, even without an epigenetic explanation, is where we should start.

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* A meme is the smallest unit of cultural expression.  No one agrees how small, or how to define it.

References

Robert Anda and Vincent Felitti, quoted in “The adverse childhood experiences study — the largest, most important public health study you never heard of,” by Jane Ellen Stevens, 2012.  https://acestoohigh.com/2012/10/03/the-adverse-childhood-experiences-study-the-largest-most-important-public-health-study-you-never-heard-of-began-in-an-obesity-clinic/

Cath Ennis, Epigenetics.  Icon Books, 2017.

Nadine Harris, The Deepest Well: Healing the Long-Term Effects of Childhood Adversity.  Houghton Mifflin/Harcourt, 2018.

Yasmin L. Hurd, et al. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacology, 2014. doi: 10.1038/npp.2013.352

Susan Strome, Heritable histones, The Scientist Magazine. https://www.the-scientist.com/daily-news/heritable-histones-36826

Rachel Yehuda and Linda Bierer, The relevance of epigenetics to PTSD: implications for the DSM-V, Journal of Traumatic Stress, 2009, vol. 22 (5): 427–434. doi:10.1002/jts.20448.

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